We request support for The Fourth International Symposium on the Biology of Vertebrate Sex Determination scheduled to take place in Kona, Hawaii, April 24-28, 2006. This meeting has the enthusiastic endorsement of the entire international community and is attended by scientists working on diverse vertebrate systems including fish, birds, reptiles, pigs, goats, horses, mice, marsupials, and humans. Some of these species rely on environmental sex determination, such as visual or population clues, or temperature of egg incubation. In contrast, all mammalian species use a genetic sex-determining system that depends on the Y-linked gene Sry. Despite this diversity, many of the same genetic pathways are involved. Surprisingly, the mechanisms of testis and ovary organogenesis are proving to be highly diverged and providing exciting insights into the evolution of developmental mechanisms. Topics of concentration at the meeting will include the evolution of sex determining mechanisms, sexual differentiation outside the gonad (including brain and other sexually dimorphic features), environmental toxins and their relation to sex differentiation disorders and infertility, the role of the gonad as a stem cell niche for germ cells, cell fate commitment and cell signaling during organogenesis of the testes and ovaries, and factors responsible for ovarian and testicular cancers. As it is nearly impossible to keep up with the advances made in so many diverse systems, the goal of this meeting is to exchange information, using comparative systems to advance our understanding of the process of sex determination and sex differentiation. A great deal of collaboration came about as a result of the first three meetings: reagents were exchanged, experiments planned and new ways of looking at sex determination discussed. We expect the fourth meeting to be as productive and stimulating as the previous three. In the past two symposia, the enrollment has been between 120-130, most of whom presented either a talk or a poster. We expect an increase this year to approximately 140-150 as the number of sex-determination laboratories has grown in the last few years, and the advances in genomic array technology and production of mutants have provided a flood of data that needs to be better integrated into the thinking in the field. Understanding how critical genes in sex determining pathways evolved and how they function in lower vertebrates is expected to improve diagnosis and treatment of human disorders. [unreadable] [unreadable] [unreadable]